Summary of findings 3. Postoperative MMC‐EMDA with sequential BCG induction and maintenance versus postoperative BCG induction and maintenance therapy for non‐muscle invasive bladder cancer.

Participants: people with non‐muscle invasive bladder cancer (pT1 or carcinoma in situ of the bladder, or both) Setting: multicentre study in Italy (all comparisons in the review stemmed from same study group) Intervention: initial 3 cycles of MMC‐EMDA with BCG intravesical instillation (cycle: 2 BCG followed by 1 MMC‐EMDA) at weekly interval about 3 weeks after TURBT, and 3 cycles of MMC‐EMDA with BCG intravesical instillations (monthly instillation, cycle: 2 MMC‐EMDA followed by 1 BCG) for 9 months Control: initial 6 BCG intravesical instillations at weekly interval about 3 weeks after TURBT, and BCG monthly instillation for 10 months
Outcomes	No of participants (studies)	Quality of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects* (95% CI)
				Risk with BCG	Risk difference with postoperative MMC‐EMDA with BCG
Time to recurrence Follow‐up: median 88 months	212 (1 RCT)	⊕⊕⊝⊝ Low1,2	HR 0.51 (0.34 to 0.77)	Study population
				581 per 1000	223 fewer per 1000 (325 fewer to 93 fewer)
				Moderate
				430 per 1000 3	181 fewer per 1000 (256 fewer to 79 fewer)
Time to progression Follow‐up: median 88 months	212 (1 RCT)	⊕⊕⊝⊝ Low1,2	HR 0.36 (0.17 to 0.75)	Study population
				215 per 1000	132 fewer per 1000 (175 fewer to 49 fewer)
				Moderate
				100 per 1000 3	63 fewer per 1000 (82 fewer to 24 fewer)
Serious adverse events Follow‐up: median 88 months	212 (1 RCT)	⊕⊝⊝⊝ Very low4,5	RR 1.02 (0.21 to 4.94)	Study population
				28 per 1000	1 more per 1000 (22 fewer to 110 more)
				High
				70 per 1000 3	1 more per 1000 (55 fewer to 276 more)
Disease‐specific survival Follow‐up: median 88 months	212 (1 RCT)	⊕⊕⊝⊝ Low1,2	HR 0.31 (0.12 to 0.80)	Study population
				159 per 1000	107 fewer per 1000 (138 fewer to 30 fewer)
				Moderate
				60 per 1000 3	41 fewer per 1000 (53 fewer to 12 fewer)
Disease‐specific quality of life ‐ not reported	‐	‐	‐	‐	‐
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). BCG: Bacillus Calmette‐Guérin; CI: confidence interval; HR: hazard ratio; MMC‐EMDA: electromotive drug administration of mitomycin C; RCT: randomised controlled trial; RR: risk ratio; TURBT: transurethral resection of bladder tumour.
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

¹ Downgrade by one level for study limitations: unclear risk of selection and attrition bias and high risk of performance and detection bias.

² Downgrade by one level for imprecision: confidence interval crossed assumed clinically meaningful threshold.

³Oddens 2013: disease recurrence, progression and disease‐specific death after TURBT with BCG maintenance therapy (once a week for 6 weeks, followed by three weekly instillations at months 3, 6 and 12) were 42.8%, 9.1% and 5.9%, respectively and stopped treatment due to local or systemic adverse events was 7% based on a long‐term median follow‐up of more than 7.1 years.

⁴ Downgrade by one level for study limitations: unclear risk of selection bias and high risk of performance and detection bias.

⁵ Downgraded by two level for imprecision: confidence interval was wide and crossed assumed clinically meaningful threshold.